Study: E-cigs increase 'superbug' MRSA resistance

Laura Crotty Alexander led a study that found the superbug MRSA becomes more resistant when exposed to electronic cigarette vapors. Crotty Alexander is a UCSD assistant clinical professor of medicine and staff physician at VA San Diego Healthcare System.
— Hayne Palmour IV

Laura Crotty Alexander led a study that found the superbug MRSA becomes more resistant when exposed to electronic cigarette vapors. Crotty Alexander is a UCSD assistant clinical professor of medicine and staff physician at VA San Diego Healthcare System.
— Hayne Palmour IV

Electronic cigarette vapor makes the antibiotic-resistant “superbug” MRSA harder to kill and reduces the immune system’s ability to fight infection, according to a study by UC San Diego and VA researchers.

If confirmed in people, the laboratory findings indicates a major potential health hazard of e-cigarettes, widely considered safer than smoking tobacco. These devices vaporize various flavored juices. These juices usually contain nicotine, the addictive chemical in tobacco.

MRSA, or methicillin-resistant Staphylococcus aureus, represents a major public health concern, especially at hospitals. The bacterium resists many antibiotics. If MRSA gets into the bloodstream or deep into the body, such as through surgery, or into the lungs, the infection can be life-threatening.

E-cigarettes first appeared on the U.S. market about seven years ago. Their potential hazards has been intensively researched, but there’s still much uncertainty. Earlier this year, researchers at UC Riverside published research showing that cinnamon flavorings can damage cells in lab tests. The study, led by UCR cell biology professor Prue Talbot, was published in the journal Toxicology in Vitro.

Last month, the U.S. Food and Drug Administration announced it would regulate the sale of e-cigarettes as tobacco products. Locally, various government agencies in San Diego County have imposed restrictions on their use. In March, the El Cajon City Council imposed the same restrictions on use and sale of e-cigarettes as apply to regular cigarettes. The Encinitas City Council has also moved in that direction, as has Oceanside.

San Diego City Councilman Mark Kersey proposes to ban their use inside Petco Park, Qualcomm Stadium and all other city facilities.

Crotty Alexander and colleagues performed several experiments to determine the effect of e-cigarette vapor on MRSA; on human and mouse cells exposed to the vapor, and in mice exposed to MRSA grown with the vapor. The experiments indicated that MRSA grown with the vapor experience stress that activates resistance mechanisms.

In mouse models of pneumonia, three times as many MRSA cells exposed to e-cigarette vapor survived in the lungs compared to a control. When the same experiment was repeated with cigarette smoke, four times as many MRSA cells survived, and the mouse mortality rate was 30 percent higher than in a control.

Other experiments examined the effect of exposure to e-cigarette vapor on the growth and hardiness of MRSA. Bacteria grown with the vapor formed thicker protective biofilms, and developed increased resistance to bacteria-killing substances called human antimicrobial peptides.

Cigarette smoke also reduces the body’s immune response and makes MRSA tougher, according to a parallel lab study by the researchers.

“We’ve known already about the cigarette smoke, but this e-cigarette vapor impact on the immune system is brand new information,” Crotty Alexander said.

Potentially, the increased resistance could increase the spread of MRSA, she said, but that needs to be determined in human clinical testing.

“These studies are all in dishes and mice so far, so it’s hard to extrapolate,” she said.

Another researcher not involved in the studies, Dr. Michael Siegel of Boston University, made the same point, using many of the same words.

“What happens in cell cultures is not always relevant to the clinical situation,” said Siegel, a professor of community health sciences. “You can’t necessarily extrapolate from what’s called an in vitro study to what would happen to an actual human being.”

Siegel said the research is best interpreted as “suggestive evidence” of a possible effect that requires human studies to be confirmed. A study conclusion that the evidence suggests e-cigarette “vapers” are more vulnerable to infection went too far.

“That’s way, way more than they can conclude from this study,” Siegel said.

Stopping resistance

The researchers are trying to find out the mechanisms for MRSA resistance and how it might be thwarted by altering the components in e-cigarette juices.

Resistance may have been encouraged by changes in alkalinity and acidity, Crotty Alexander said. Cells cultured with the vapors became excessively alkaline, increasing from a pH 7.4 to 8.4, and then became excessively acidic. This appears to be an inherent property of nicotine, she said. Nicotine itself is an alkaloid compound.

Other experiments examined the effect of e-cigarette vapor on human epithelial cells, the kind that line the lungs and on mouse immune cells found in the lungs called alveolar macrophages. Exposure reduced the ability of these cells to kill MRSA compared to control cells not exposed.

The immune-suppressing effects on the nonbacterial cells may be caused by something other than nicotine, she said.

“I think it would be really cool if we could find a way for people to use these in a safe way,” she said. “We are looking at different components of the e-cigarette juices to try and find the problems within the juices. They do have juices that don’t have nicotine, so we’re testing those as well.”

Testing the juices is a major effort, Crotty Alexander said. The researchers tested about six flavors, including cappuccino, crème brûlée and chocolate mint. But there’s far more that haven’t been tested, from many sources.

“There’s over 200 companies producing these juices,” she said.

The study was funded by the VA with support from UCSD. For more information on the study, contact Crotty Alexander at lcrotty@ucsd.edu.